Bias and Precision in Magnetic Resonance Imaging-Based Estimates of Renal Blood Flow: Assessment by Triangulation.

BACKGROUND: Renal blood flow (RBF) can be measured with dynamic contrast enhanced-MRI (DCE-MRI) and arterial spin labeling (ASL). Unfortunately, individual estimates from both methods vary and reference-standard methods are not available. A potential solution is to include a third, arbitrating MRI method in the comparison. PURPOSE: To compare RBF estimates between ASL, DCE, and phase contrast (PC)-MRI. STUDY TYPE: Prospective. POPULATION: Twenty-five patients with type-2 diabetes (36% female) and five healthy volunteers (HV, 80% female). FIELD STRENGTH/SEQUENCES: A 3 T; gradient-echo 2D-DCE, pseudo-continuous ASL (pCASL) and cine 2D-PC. ASSESSMENT: ASL, DCE, and PC were acquired once in all patients. ASL and PC were acquired four times in each HV. RBF was estimated and split-RBF was derived as (right kidney RBF)/total RBF. Repeatability error (RE) was calculated for each HV, RE = 1.96 × SD, where SD is the standard deviation of repeat scans. STATISTICAL TESTS: Paired t-tests and one-way analysis of variance (ANOVA) were used for statistical analysis. The 95% confidence interval (CI) for difference between ASL/PC and DCE/PC was assessed using two-sample F-test for variances. Statistical significance level was P < 0.05. Influential outliers were assessed with Cook's distance (Di > 1) and results with outliers removed were presented. RESULTS: In patients, the mean RBF (mL/min/1.73m2 ) was 618 ± 62 (PC), 526 ± 91 (ASL), and 569 ± 110 (DCE). Differences between measurements were not significant (P = 0.28). Intrasubject agreement was poor for RBF with limits-of-agreement (mL/min/1.73m2 ) [-687, 772] DCE-ASL, [-482, 580] PC-DCE, and [-277, 460] PC-ASL. The difference PC-ASL was significantly smaller than PC-DCE, but this was driven by a single-DCE outlier (P = 0.31, after removing outlier). The difference in split-RBF was comparatively small. In HVs, mean RE (±95% CI; mL/min/1.73 m2 ) was significantly smaller for PC (79 ± 41) than for ASL (241 ± 85). CONCLUSIONS: ASL, DCE, and PC RBF show poor agreement in individual subjects but agree well on average. Triangulation with PC suggests that the accuracy of ASL and DCE is comparable. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Imaging biomarker roadmap for cancer studies.

Imaging biomarkers (IBs) are integral to the routine management of patients with cancer. IBs used daily in oncology include clinical TNM stage, objective response and left ventricular ejection fraction. Other CT, MRI, PET and ultrasonography biomarkers are used extensively in cancer research and drug development. New IBs need to be established either as useful tools for testing research hypotheses in clinical trials and research studies, or as clinical decision-making tools for use in healthcare, by crossing 'translational gaps' through validation and qualification. Important differences exist between IBs and biospecimen-derived biomarkers and, therefore, the development of IBs requires a tailored 'roadmap'. Recognizing this need, Cancer Research UK (CRUK) and the European Organisation for Research and Treatment of Cancer (EORTC) assembled experts to review, debate and summarize the challenges of IB validation and qualification. This consensus group has produced 14 key recommendations for accelerating the clinical translation of IBs, which highlight the role of parallel (rather than sequential) tracks of technical (assay) validation, biological/clinical validation and assessment of cost-effectiveness; the need for IB standardization and accreditation systems; the need to continually revisit IB precision; an alternative framework for biological/clinical validation of IBs; and the essential requirements for multicentre studies to qualify IBs for clinical use.

Prediction and assessment of responses to renal artery revascularization with dynamic contrast-enhanced magnetic resonance imaging: a pilot study.

The aim of this study was to assess the potential of dynamic contrast-enhanced (DCE) MRI to predict and evaluate functional outcomes after renal artery revascularization for renal artery stenosis (RAS). The single-kidney glomerular filtration rate (SK-GFR) was measured in 15 patients with atherosclerotic RAS with DCE-MRI and radioisotopes at baseline and 4 mo after revascularization. DCE-MRI also produced measurements of blood flow, blood volume, extraction fraction, tubular transit time, and functional volume. Stented kidneys (n = 22) were divided into three response groups on the basis of the changes in radioisotope SK-GFR: improved (n = 5), stable (n = 13), and deteriorated (n = 4). A good agreement was found between SK-GFR values from DCE-MRI and radioisotopes (correlation coefficient: 0.91). Before intervention, kidneys that improved had lower extraction fraction, higher blood volume, longer tubular transit time, and lower SK-GFR. After intervention, improved kidneys had increased functional volume, and deteriorated kidneys had reduced functional volume and extraction fraction. Revascularization improved blood flow and blood volume in all groups. This pilot study led to the hypothesis that well-vascularized kidneys with reduced extraction fractions are most likely to benefit from revascularization. More generally, DCE-MRI has the potential to replace radioisotope measurement of SK-GFR and may improve patient management by providing additional information on tissue perfusion.

Assessment of bladder motion for clinical radiotherapy practice using cine-magnetic resonance imaging.

PURPOSE: Organ motion is recognized as the principal source of inaccuracy in bladder radiotherapy (RT), but there is currently little information on intrafraction bladder motion. METHODS AND MATERIALS: We used cine-magnetic resonance imaging (cine-MRI) to study bladder motion relevant to intrafraction RT delivery. On two occasions, a 28 minute cine-MRI sequence was acquired from 10 bladder cancer patients and 5 control participants immediately after bladder emptying, after abstinence from drinking for the preceding hour. From the resulting cine sequences, bladder motion was subjectively assessed. To quantify bladder motion, the bladder was contoured in imaging volume sets at 0, 14, and 28 min to measure changes to bladder volumes, wall displacements, and center of gravity (COG) over time. RESULTS: The dominant source of bladder motion during imaging was bladder filling (up to 101% volume increase); rectal and small bowel movements were transient, with minimal impact. Bladder volume changes were similar for all participants. However for bladder cancer patients, wall displacements were larger (up to 58 mm), less symmetrical, and more variable compared with nondiseased control bladders. CONCLUSIONS: Significant and individualized intrafraction bladder wall displacements may occur during bladder RT delivery. This important source of inaccuracy should be incorporated into treatment planning and verification.

What levels of precision are achievable for quantification of perfusion and capillary permeability surface area product using ASL?

We examine the use of arterial spin labeling (ASL) in normal brains of rats and humans to measure perfusion (F) and capillary permeability surface area product (PS) using a previously described two-compartment model. We investigate the experimental limits on F and PS quantification using simulations and experimental verification in rat brain at 9.4T. A sensitivity analysis on the two-compartment model is presented to estimate optimal experimental inversion times (TIs) for F and PS quantification and indicate how sensitive the model would be to changes in F and PS. We present the expected error on flow-sensitive alternating inversion recovery (FAIR)-based F and PS measurements and quantify the precision with which these parameters could be estimated at various signal-to-noise ratios (SNRs). Perfusion was measured in four rat brains using FAIR ASL, and we conclude that perfusion could be quantified with an acceptable level of precision using this technique. However, we found that to measure PS with even a 100% coefficient of variation (CV) would require an SNR increase of approximately 2 orders of magnitude over our acquired data. We conclude that with current MR capabilities and with the experimental approach used in this study, acceptable levels of precision in the measurement of PS are not possible.